IL28B polymorphisms influence stage of fibrosis and spontaneous or interferon-induced viral clearance in thalassemia patients with hepatitis C virus infection

• Published in: Haematologica (Roma) 2012-05, Vol.97 (5), p.679-686
• Main Authors: DI MARCO, Vito, BRONTE, Fabrizio, FIORENZA, Flavia, GERARDI, Calogera, GRIMAUDO, Stefania, DI CRISTINA, Antonietta, LEVRERO, Massimo, CRAXI, Antonio, CALVARUSO, Vincenza, CAPRA, Marcello, BORSELLINO, Zelia, MAGGIO, Aurelio, CONCETTA RENDA, Maria, PITROLO, Lorella, LO PINTO, Maria Carmela, RIZZO, Michele
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Anemias. Hemoglobinopathies; Antibodies, Viral - immunology; Antiviral Agents - therapeutic use; beta-Thalassemia - drug therapy; beta-Thalassemia - genetics; beta-Thalassemia - virology; Biological and medical sciences; Cohort Studies; Diseases of red blood cells; Female; Follow-Up Studies; Gastroenterology. Liver. Pancreas. Abdomen; Hematologic and hematopoietic diseases; Hepacivirus - genetics; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - genetics; Hepatitis C, Chronic - virology; Human viral diseases; Humans; Infectious diseases; Interferon Inducers - therapeutic use; Interferon-alpha - therapeutic use; Interferons; Interleukins - genetics; Liver Cirrhosis - etiology; Liver Cirrhosis - pathology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Original and Brief Reports; Other diseases. Semiology; Polymorphism, Single Nucleotide - genetics; Prognosis; Viral diseases; Viral hepatitis; Viral Load - genetics; Young Adult
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2011.050351

Polymorphisms in the interleukin-28B are important determinants in the spontaneous and drug-induced control of hepatitis C virus infection. We assessed the association of rs8099917 and rs12979860 polymorphisms with spontaneous viral clearance, severity of liver fibrosis, and response to interferon-monotherapy in 245 thalassemia major patients with hepatitis C virus infection. Ninety-eight patients (40%) had a spontaneous viral clearance while 147 patients (60%) developed a chronic infection. Spontaneous viral clearance was more frequent among patients with the T/T genotype of rs8099917 polymorphism (OR 2.130; P = 0.008) or C/C genotype of rs12979860 polymorphism (OR 2.425; P = 0.001). During observation, 131 patients with chronic infection underwent a liver biopsy; age (OR 1.058; P = 0.01) G/T or G/G genotypes of rs8099917 polymorphism (OR 3.962; P = 0.001), and C/T or T/T genotypes of rs12979860 polymorphism (OR 3.494; P = 0.005) were associated with severe liver fibrosis, independent of liver iron concentration. Finally, T/T genotype of rs8099917 polymorphism (OR 3.014; P = 0.03) or C/C genotype of rs12979860 polymorphism (OR 3.285; P = 0.01), age (OR 0.902; P = 0.001), female gender (OR 3.418; P = 0.01) and 2 or 3 virus C genotypes (OR 4.700; P=0.007) were independently associated with sustained virological response in 114 patients treated with alpha-interferon. Conclusions Polymorphisms in the interleukin-28B are associated with the control of hepatitis C virus infection in thalassemia major patients, and understanding allelic patterns has an important role in determining prognosis and therapeutic management.